title: Lipogenic enzymes as therapeutic targets for obesity and diabetes.
abstract: Since storage of excess fat in peripheral tissues is a contributing factor leading to obesity and type II diabetes, many investigators are studying the key lipid metabolizing enzymes found in adipose tissue as drug targets to reduce excess fat. The availability of cultured cell lines and primary stem cells, preadipocyetes, and adipocytes has facilitated therapeutic approaches aimed at targeting fat storage. This includes developing inhibitors for enzymes regulating lipogenesis in these cells, such as acetyl-CoA carboxylase, fatty acid synthase, diacylgycerol acyl transferase, and stearoyl CoA desaturase. High level expression of each protein is often used to confirm stem cells have undergone adipogenesis. Inhibition of these enzymes often leads to reduced fat cell fat differentiation and lipid synthesis and may also contribute to increased fat oxidation and energy expenditure. This article reviews developments in pharmaceutical research on these enzymes, with particular emphasis on the role of the enzymes in adipose tissue metabolism.
authors.affiliation: Cardiovascular and Metabolic Research, Johnson and Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Springhouse, PA 19477, USA. Jlenhar1@its.jnj.com
authors.forename: James M
authors.initials: JM
authors.lastname: Lenhard
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017667:Adipocytes / Q000201:enzymology* / Q000378:metabolism; D050156:Adipogenesis; D000273:Adipose Tissue / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D050155:Lipogenesis; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013230:Stearoyl-CoA Desaturase; D051048:Diacylglycerol O-Acyltransferase; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase